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Home , Roderick MacKinnon

CURRICULUM VITAE

Name: Roderick MacKinnon

Address: Laboratory of Molecular Neurobiology and HHMI/The P.O. Box 47 1230 York Avenue New York, NY 10021

Date of Birth: , 1956

Place of Birth: Melrose, Massachusetts

Education:

1978 B.A. () 1982 M.D. School of Medicine

Postdoctoral Training:

1985-86 NIH Postdoctoral Fellow, Department of Medicine, Beth Israel Hospital, , Boston, MA 1986-89 NIH Postdoctoral, Department of Biochemistry, Brandeis University, Waltham, MA

Academic and Hospital Appointments:

1982-85 Medical House Officer, Internal Medicine, Beth Israel Hospital/, Boston, MA 1989-91 Assistant Professor, Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 1991-92 Assistant Professor, Department of Neurobiology, Harvard Medical School, Boston, MA 1992-95 Associate Professor, Department of Neurobiology, Harvard Medical School, Boston, MA 1995-96 Professor, Department of Neurobiology, Harvard Medical School, Boston, MA 1996-present Professor, Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, New York, NY 1997-present Investigator, Howard Hughes Medical Institute.

Awards and Honors:

1978 High Honors in Biochemistry, Brandeis University 1982 Alpha Omega Alpha Medical Honors Society, Tufts University School of Medicine 1992 PEW Scholar in the Biomedical Sciences 1992 McKnight Scholars Award 1995 Biophysical Society Young Investigator Award 1997 McKnight Investigator Award 1998 W. Alden Spencer Award, Columbia University 1998 AAAS Newcomb Cleveland Prize 1999 Albert Lasker Basic Medical Research Award 2000 Lewis S. for Distinguished Work in Basic Medical Research 2000 Hodgkin-Huxley-Katz Prize 2000 Alexander M. Cruickshank Award 2000 Membership to the U.S. National Academy of Sciences 2001 Gairdner Foundation International Award 2001 Perl-UNC Prize 2002 The Degree of Doctor of Science, Honoris Causa – Tufts University 2003 Fritz Lipmann Lectureship Award 2003 in 2003 Louisa Gross Horwitz Prize 2003 Scientific American Research Leader of the Year 2004 Max Tishler Prize – Harvard University 2004 National Lecturer, Biophysical Society Annual Meeting 2004 Bijvoet Medal for Outstanding Research – The Netherlands 2005 The Hans Neurath Award-Protein Society 2005 The Degree of Doctor of Science, Honoris Causa – Brandeis University 2005 Membership to the American Philosophical Society 2006 Rolf Sammet Honorary Lectureship –J.W. Goethe University, Frankfurt, Germany 2006 The Degree of Doctor of Science, Honoris Causa – Pohang University Of Science and Technology, Korea

BIBLIOGRAPHY

1) MacKinnon R, Morgan JP (1986) Influence of the thyroid state on the transient in ventricular muscle. Pflugers Arch. 407: 142-144

2) MacKinnon R, Gwathmey J, Morgan JP (1987) Differential effects of reoxygenation on intracellular calcium and isometric tension. Pflugers Arch. 409: 448-453

3) MacKinnon R, Gwathmey J, Allen P, Briggs M, Morgan JP (1988) Modulation by the thyroid state of intracellular calcium and contractility in ferret ventricular muscle. Circ. Res. 63: 1080-1089.

4) Anderson CS, MacKinnon R, Smither C, Miller C (1988) Charybdotoxin block of single Ca2+- activated K+ channels: Effects of channel gating, voltage, and ionic strength. J. Gen. Physiol. 91: 317-333

5) MacKinnon R, Miller C (1988) Mechanism of charybdotoxin block of the high-conductance Ca2+-activated K+ channel. J. Gen. Physiol. 91: 335-349

6) MacKinnon R, Reinhart P, White M (1988) Charybdotoxin block of Shaker K+ channels suggests that different types of K+ channels share common structural features. Neuron 1: 997-1001

7) MacKinnon R, Miller C (1989) Functional modification of Ca2+-activated K+ channel by trimethyloxonium. Biochemistry 28: 8087-8092

8) MacKinnon R, Latorre R, Miller C (1989) The role of surface electrostatics in the operation of a high-conductance Ca2+-activated K+ channel. Biochemistry 28: 8092-8099

9) MacKinnon R, Miller C (1989) Mutant K+ channels with altered binding of charybdotoxin, a pore-blocking peptide inhibitor. Science 245: 1382-1385

10) Schumaker M, MacKinnon R (1990) A simple model for multi-ion permeation: single- vacancy conduction in a simple pore model. Biophysical J. 58: 975-984

11) MacKinnon R, Heginbotham L, Abramson T (1990) Mapping the receptor site for charybdotoxin, a pore-blocking inhibitor. Neuron 5: 767-771

12) MacKinnon R, Yellen G (1990) Mutations affecting TEA blockade and ion permeation in voltage-activated K+ channels. Science 250: 276-279

13) Yellen G, Jurman M, Abramson T, MacKinnon R (1991) Mutations affecting TEA blockade identify the probable pore-forming region of a K+ channel. Science 251: 939-942

14) MacKinnon R (1991) Determination of the subunit stoichiometry of a voltage-dependent potassium channel. Nature 350: 232-235

15) Heginbotham L, MacKinnon R (1992) The aromatic binding site for tetraethylammonium on potassium channels. Neuron 8: 483-491

16) Heginbotham L, Abramson T, MacKinnon R (1992) A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels. Science 258: 1152-1155

17) Escobar L, Root M, MacKinnon R (1993) Influence of protein surface charge on the bimolecular kinetics of a potassium channel peptide inhibitor. Biochemistry 32: 6982-6987

18) Perozo E, MacKinnon R, Bezanilla F, Stefani E (1993) Gating currents from a nonconducting mutant reveal open-closed conformations in Shaker K+ channels. Neuron 11: 353-358

19) Root M, MacKinnon R (1993) Identification of an external divalent cation-binding site in the pore of a cGMP-activated channel. Neuron 11: 459-466

20) Heginbotham L, MacKinnon R (1993) Conduction properties of the cloned Shaker K+ channel. Biophysical J. 65: 2089-2096

21) MacKinnon R, Aldrich RW, Lee AW (1993) Functional stoichiometry of Shaker potassium channel inactivation. Science 262: 757-759

22) Heginbotham L, Lu Z, Abramson T, MacKinnon R (1994) Mutations in the K+ channel signature sequence. Biophysical J. 66: 1061-1067

23) Garcia ML, Garcia-Calvo M, Hidalgo P, Lee A, MacKinnon R (1994) Purification and characterization of three inhibitors of voltage-dependent K+ channels from Leiurus Quin questriatus var. Hebraeus venom. Biochemistry 33: 6834-6839

24) Lu Z, MacKinnon R (1994) A conductance maximum observed in an inward-rectifier potassium channel. J. Gen. Physiol. 104: 477-486

25) Root MJ, MacKinnon R (1994) Two identical noninteracting sites in an revealed by proton transfer. Science 265: 1852-1856

26) Lu Z, MacKinnon R (1994) Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+ channel. Nature 371: 243-246

27) Gross A, Abramson T, MacKinnon R (1994) Transfer of toxin receptor to an insensitive potassium channel. Neuron 13: 961-966

28) Hidalgo P, MacKinnon R (1995) Revealing the architecture of a K+ channel pore through mutant cycles with a peptide inhibitor. Science 268: 307-310

29) Krezel A, Khasibhatla C, Hidalgo P, MacKinnon R, Wagner G (1995) Solution structure of the K+ channel inhibitor agitoxin 2: Caliper for probing channel geometry. Protein Science 4: 1478-1489

30) Swartz K, MacKinnon R (1995) An Inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula. Neuron 15: 941-949

31) Lu Z, MacKinnon R (1995) Probing a potassium channel pore with an engineered protonatable site. Biochemistry 34: 13133-13138

32) Park C-S, MacKinnon R (1995) Divalent cation selectivity in a cyclic nucleotide-gated ion channel. Biochemistry 34: 13328-13333

33) Ranganathan R, Lewis J, MacKinnon R (1996) Spatial localization of the K+ channel selectivity filter by mutant cycle-based structure analysis. Neuron 16: 131-139

34) Gross A, MacKinnon R (1996) Agitoxin footprinting the Shaker potassium channel pore. Neuron 16: 399-406

35) Aggarwal SK, MacKinnon R (1996) Contribution of the S4 segment to gating charge in the Shaker potassium channel. Neuron 16: 1169-1177

36) Doyle DA, Lee A, Lewis J, Kim E, Sheng M, MacKinnon R (1996) Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. Cell 85: 1067-1076

37) Swartz KJ, MacKinnon R (1997) Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites. Neuron 18: 665-673

38) Swartz KJ, MacKinnon R (1997) Mapping the receptor site for Hanatoxin, a gating modifier of voltage-dependent K+ channels. Neuron 18: 675-682

39) Lu Z, MacKinnon R (1997) Purification, characterization, and synthesis of an inward- rectifier K+ channel inhibitor from scorpion venom. Biochemistry 36: 6936-6940

40) Doyle DA, Cabral JM, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R (1998) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280: 69-77

41) MacKinnon R, Cohen SL, Kuo A, Lee A, Chait BT (1998) Structural conservation in prokaryotic and eukaryotic potassium channels. Science 280: 106-109

42) Imredy J, Chen C, MacKinnon R (1998) A snake toxin inhibitor of inward rectifier potassium channel ROMK1. Biochemistry 37: 14867-14874

43) Cabral JMH, Lee A, Cohen SL, Chait BT, Li M, MacKinnon R (1998) Crystal structure and functional analysis of the HERG K+ channel N-terminus: a eukaryotic PAS domain. Cell 95: 649-655

44) Gulbis JM, Mann S, MacKinnon R (1999) Structure of a voltage-dependent K+ channel subunit. Cell 97: 943-952

45) Roux B, MacKinnon R (1999) The cavity and pore helices in the KcsA K+ channel: electrostatic stabilization of monovalent cations. Science 285: 100-102

46) Morrill JA, MacKinnon R, (1999) Isolation of a single carboxyl-carboxylate proton binding site in the pore of a cyclic nucleotide-gated channel. J. Gen. Physiol 114: 71-84

47) Imredy JP, MacKinnon R, (2000) Energetic and structural interactions between δ-dendrotoxin and voltage-gated potassium channel. J. Mol. Biology 296: 1283-1294

48) Jiang Y, MacKinnon R, (2000) The barium site in a potassium channel by x-ray crystallography. J. Gen. Physiol 115: 269-272

49) Gulbis JM, Zhou M, Mann S, MacKinnon R (2000) Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels. Science 289: 123-127

50) Jiang Y, Pico A, Cadene M, Chait B, MacKinnon R (2001) Structure of the RCK domain from the E. coli K+ channel and demonstration of its presence in the human BK channel. Neuron 29: 593-601

51) Zhou M, Morais-Cabral J, Mann S, MacKinnon R (2001) Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors. Nature 411: 657-661

52) Morais-Cabral JH, Zhou Y, MacKinnon R. (2001) Energetic optimization of ion conduction rate by the K+ selectivity filter. Nature 414:37-42

53) Zhou Y, Morais-Cabral JH, Kaufman A, MacKinnon R (2001) Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 Å resolution. Nature 414: 43-48

54) Dutzler R, Campbell EB, Cadene M, Chait BT, MacKinnon R (2002) X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity. Nature 415: 287-294

55) Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R (2002) Crystal structure and mechanism of a calcium-gated potassium channel. Nature 417: 515-522

56) Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R (2002) The open pore conformation of potassium channels. Nature 417: 523-526

57) Valiyaveetil FI, MacKinnon R, Muir TW (2002) Semisynthesis and folding of the potassium channel KcsA. J. Am. Chem. Soc. 124 (31): 9113-9120

58) Valiyaveetil FI, Zhou Y, MacKinnon R (2002) Lipids in the structure, folding, and function of the KcsA K(+) channel. Biochemistry 41 (35): 10771-10777

59) Yifrach O, MacKinnon R (2002) Energetics of pore opening in a voltage-gated K+ channel. Cell 111: 231-239

60) Nishida M, MacKinnon R (2002) Structural basis of inward rectification: Cytoplasmic pore of the G-protein gated inward rectifier GIRK1 at 1.8 Å resolution. Cell 111: 957-965

61) Ruta V, Jiang Y, Lee A, Chen J, MacKinnon R (2003) Functional analysis of an archaebacterial voltage-dependent K+ channel. Nature 422: 180-185

62) Dutzler R, Campbell EB, MacKinnon R (2003) Gating the selectivity filter in ClC chloride channels. Science 300: 108-112

63) Jiang Y, Lee A, Chen J, Ruta V, Cadene M, Chait BT, MacKinnon R (2003) X-ray structure of a voltage-dependent K+ channel. Nature 423: 33-41

64) Jiang Y, Ruta V, Chen J, Lee A, MacKinnon R (2003) The principle of gating charge movement in a voltage-dependent K+ channel. Nature 423: 42-48

65) Zhou Y, MacKinnon R (2003) The occupancy of ions in the K(+) selectivity filter: charge balance and coupling of ion binding to a protein conformational change underlie high conduction rates. J. Mol. Biol. 333 (5): 965-975

66) Sekedat M, Valiyaveetil F, MacKinnon R, Muir TW (2003) Semisynthesis of the potassium channel KcsA. Biopolymers 71 (3): 364-365

67) MacKinnon R (2003) Potassium channels. FEBS Letter 555 (1): 62-65

68) Zhou Y, MacKinnon R (2004) Ion binding affinity in the cavity of the KcsA potassium channel. Biochemistry. 43(17): 4978-4982

69) Zhou M, MacKinnon R (2004) A mutant KcsA K+ channel with altered conduction properties and selectivity filter ion distribution. J. Mol. Biol. 338(4): 839-846

70) Valiyaveetil FI, Sekedat M, Muir TW, MacKinnon R (2004) Semi-synthesis of a functional K+ channel. Angew. Chem.Int. Ed. Engl. 43(19): 2504-2507

71) Lee SY, MacKinnon R (2004) A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom. Nature 430: 232-235

72) Jiang QX, Wang DN, MacKinnon R (2004) Electron microscopic analysis of KvAP voltage- dependent K+ channels in an open conformation. Nature 430: 806-810

73) Valiyaveetil FI, Sekedat M, Muir TW, MacKinnon R (2004) Glycine as a D-amino acid surrogate in the selectivity filters of K+ channels. Proc. Natl. Acad. Sci. U. S. A. 101(49):17045-17049

74) Ruta V, MacKinnon R (2004) Localization of the voltage-sensor toxin receptor on KvAP. Biochemistry 43 (31): 10071-10079

75) MacKinnon R (2004) Potassium channels and the atomic basis of selective ion conduction (Nobel Lecture). Angew. Chem. Int. Ed. Engl. 43(33): 4265-4277

76) Ohndorf UM, MacKinnon R (2005) Construction of a Cyclic Nucleotide-Gated KcsA K+ Channel. J. Mol. Biol. 350 (5): 857-865

77) Long SB, Campbell EB, MacKinnon R (2005) Crystal structure of a mammalian voltage- dependent Shaker family K+ channel. Science 309 (5736): 897-903

78) Long SB, Campbell EB, MacKinnon R (2005) Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science 309 (5736): 903-908

79) Ruta V, Chen JY, MacKinnon R (2005) Calibrated Measurement of Gating Charge Arginine Displacement in the KvAP Voltage-Dependent K+ Channel. Cell 123 (3): 463-475

80) Lee SY, Lee A, Chen JY, MacKinnon R (2005) Structure Of The KvAP Voltage-Dependent K+ Channel And Its Dependence On The Lipid Membrane. PNAS 102 (43): 15441-15446

81) Gouaux E, MacKinnon R (2005) Principles of selective ion transport in channels and pumps. Science 310 (5753): 1461-1465

82) Valiyaveetil FI, Sekedat M, MacKinnon R, Muir TW (2006) Structural and Functional Consequences of an Amide-to-Ester Substitution in the Selectivity Filter of a Potassium Channel. J. Am. Chem. Soc. 128 (35): 11591-11599

83) Valiyaveetil FI , Leonetti M, Muir TW, MacKinnon R (2006) Ion selectivity in a semisynthetic K+ channel locked in the conductive conformation. Science 314 (5801): 1004- 1007

84) Schmidt D, Jiang QX, MacKinnon R (2006) Phospholipids and the origin of cationic gating charges in voltage sensors. Nature 444: 775-779

85) Lockless SW, Zhou M, MacKinnon R (2007) Structural and Thermodynamic Properties of Selective Ion Binding in a K+ Channel. PLoS Biol 5(5): e121